Circulation. 2005;112:2377
(Circulation. 2005;112:2377.)
© 2005 American Heart Association, Inc.
Issue Highlights
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CORIN GENE MINOR ALLELE DEFINED BY 2 MISSENSE MUTATIONS IS COMMON IN BLACKS AND ASSOCIATED WITH HIGH BLOOD PRESSURE AND HYPERTENSION, by Dries et al.
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Natriuretic peptides play a fundamental role in blood pressure
regulation. Recent work has emphasized the importance of corin,
an enzyme that cleaves pro-natriuretic peptides to their active
forms. In this issue of
Circulation, Dries and colleagues relate
a single nucleotide polymorphism of the corin gene (that is
common in blacks but rare in whites) to hypertension prevalence
and blood pressure levels in black patients in the Dallas Heart
Study sample. The presence of the corin I555 allele was associated
with 63% higher odds of prevalent hypertension and higher systolic
blood pressure (relative to those without the variant). Two
additional features of this study are noteworthy. First, the
authors addressed potential confounding by population stratification:
If subjects are sampled from 2 or more subpopulations or from
recently admixed populations (such as blacks), for which the
frequencies of disease-susceptibility alleles differ, spurious
associations may arise. Therefore, the authors genotyped more
than 2000 single nucleotide polymorphisms highly informative
of ancestry and adjusted for "estimated ancestry" in multivariable
analyses. The association of the corin variant with hypertension
remained robust upon adjustment for ancestry. Second, recognizing
the importance of validating genotype-phenotype associations
to minimize false positive findings, they replicated their findings
in 2 other cohorts. See p
2403.
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ANGIOTENSIN RECEPTOR BLOCKADE AND EXERCISE CAPACITY IN ADULTS WITH SYSTEMIC RIGHT VENTRICLES: A MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED CLINICAL TRIAL, by Dore et al.
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It is unknown whether pharmacological blockade of the renin-angiotensin
system has beneficial effects in patients with complex congenital
heart disease in whom the morphological right ventricle supports
the systemic circulation. Dore and colleagues performed a multicenter,
randomized, double-blind, placebo-controlled crossover trial
to assess the effects of losartan on exercise capacity and neurohormonal
levels in 29 patients with systemic right ventricles due to
D-transposition of the great arteries with a Mustard baffle
or congenitally corrected transposition. Despite impairments
in baseline functional testing, adult patients with a systemic
right ventricle did not improve their exercise capacity with
losartan therapy. Minimal baseline activation of the renin-angiotensin
system may explain this lack of benefit. Caution is warranted
in extrapolating results from studies assessing effects of inhibition
of the renin-angiotensin system on the failing left ventricle
without independent validation on the systemic right ventricle.
See p
2411.
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EFFECT ON SURVIVAL AND HOSPITALIZATION OF INITIATING TREATMENT FOR CHRONIC HEART FAILURE WITH BISOPROLOL FOLLOWED BY ENALAPRIL, AS COMPARED WITH THE OPPOSITE SEQUENCE: RESULTS OF THE RANDOMIZED CARDIAC INSUFFICIENCY BISOPROLOL STUDY (CIBIS) III TRIAL, by Willenheimer et al.
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Clinicians managing patients with heart failure frequently prescribe
an ACE inhibitor as one of the first drugs and titrate the dose
up to the maximum tolerated. Other drugs shown to be helpful
in heart failure that are started subsequently may not be titrated
as aggressively. The CIBIS III investigators randomized 1010
patients with mild to moderate heart failure to 6 months of
therapy with either bisoprolol or enalapril to determine if
initiation of a ß-blocker first would yield outcomes
comparable to those achieved by initiation of an ACE inhibitor
first. Noninferiority of bisoprolol-first therapy was shown
in an intention-to-treat analysis, which suggests that physicians
now have data to support a customized approach to management
of heart failure with initiation of either a ß-blocker
or an ACE inhibitor first, according to clinical circumstances.
The CIBIS III trial was presented at a Hotline Session of the
ESC Congress 2005 and published online simultaneously in
Circulation.
This print version of the paper is accompanied by an editorial
to help place the findings in perspective. See pp
2380 and
2426.
Visit http://www.circ.ahajournals.org:
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Images in Cardiovascular Medicine
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Culprit Lesion Atherothrombectomy During Acute Myocardial Infarction:
Extraction of an Acute Coronary Plaque Rupture. See p
e267.
Delayed Contrast-Enhanced Magnetic Resonance Imaging in Pulmonary Arterial Hypertension. See p e268.
Anterolateral Papillary Muscle Rupture Complicated by the Obstruction of a Single Diagonal Branch. See p e269.
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Correspondence
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See p
e271.
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